Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study. / 在2019å† çŠ¶ç— æ¯’ç— æš´å‘æµè¡ŒæœŸé—´æ„ŸæŸ“å¹¶ä½é™¢æ²»ç–—çš„è‚¾ç§»æ¤å—è€ çš„ä¸´åºŠç‰¹å¾ä¸Žé¢„åŽï¼š ä¸€é¡¹ä¸­å›½å•ä¸­å¿ƒé˜Ÿåˆ—ç ”ç©¶.

BACKGROUND: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. METHODS: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. RESULTS: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)|-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. CONCLUSIONS: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.

Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.

Background: The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection. Methods: This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months. Results: Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months. Conclusion: Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.

Outcomes of allograft from donor kidney microthrombi and secondary recipient thrombotic microangiopathy: should we consider loosening the belt? / ä¾›ä½“è‚¾å¾®è¡€æ “å’Œç»§å‘æ€§å—ä½“è¡€æ “æ€§å¾®è¡€ç®¡ç— å¯¹åŒç§å¼‚ä½“ç§»æ¤è‚¾çš„å½±å“ï¼šæˆ‘ä»¬åº”è¯¥æ”¾æ¾è­¦æƒ•å—ï¼Ÿ.

There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.

Wide-spectrum antibiotic prophylaxis guarantees optimal outcomes in drowned donor kidney transplantation.

BACKGROUND: Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. RESEARCH DESIGN AND METHODS: This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. RESULTS: Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. CONCLUSIONS: Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.

Efficacy and safety of roxadustat in the treatment of renal allograft anemia patients: a case series.

BACKGROUND: To observe the efficacy and safety of roxadustat, an inhibitor of proline hydroxylase, in renal allograft anemia patients. METHODS: This prospective study collected the clinical data of renal transplant patients treated with roxadustat for anemia at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from April to August 2020. The patients were followed up every 2 weeks, and the changes in their hemoglobin index and any adverse reactions were recorded during 10 weeks of treatment. The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment. Rates of treatment response and achievement of the standard hemoglobin level were statistically analyzed. In addition, any potential adverse events and the glomerular filtration rate were recorded for 10 weeks to assess the safety of roxadustat in renal allograft anemia patients. RESULTS: After 10 weeks of roxadustat treatment, the mean hemoglobin level was 10.4±3.9 g/dL, which was significantly higher than at baseline. Over the entire period, treatment was observed to have a therapeutic effect at weeks 2-4, with mean hemoglobin levels increasing as treatment time increased. At the 10-week endpoint, the percentage of patients reaching the standard hemoglobin level and exhibiting a response to treatment was 52.4% and 71.4%, respectively. During the treatment, there was no rejection, and the glomerular filtration rate was stable. Only one person showed symptoms of fatigue, and there were no other obvious adverse reactions reported. CONCLUSIONS: Roxadustat significantly improves hemoglobin levels and can be safely used in renal transplant anemia patients.

Donor-Derived Human Parvovirus B19 Infection in Kidney Transplantation.

Background: Donor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown. Methods: This retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced. Results: A total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually. Conclusion: The incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable.

Foscarnet Therapy for Pure Red Cell Aplasia Related to Human Parvovirus B19 Infection in Kidney Transplant Recipients: A Preliminary Exploration.

BACKGROUND: Parvovirus B19-associated pure red cell aplasia (PVB19-PRCA) is an uncommon but serious complication after kidney transplantation. Currently, intravenous immunoglobulin (IVIG) is preferred as the first-line treatment for PVB19-PRCA, but presents with disadvantages of disease recurrence and expensive cost. In this context, we propose that foscarnet therapy for kidney transplantation recipients (KTR) with PVB19-PRCA may be an alternative scenario. No related study has been reported, and we performed this study to assess the efficacy and safety of foscarnet for PVB19-associated PRCA in KTR. METHODS: We conducted a retrospective review of PVB19-PRCA in KTR at our center over 9-year period. The data on therapy and outcomes in all cases treated with foscarnet are detailed records and summarized. RESULTS: Among our 68 patients, PVB19-PRCA was confirmed in 50 based on inclusion/exclusion criteria. All patients presented with refractory anemia and low reticulocyte percentage (<0.5%), the mean hemoglobin of patients was 79.8±12.6g/L at the time of PVB19-PRCA was identified. The median serum genome copy number of parvovirus B19 at diagnosis was 9.6 log10 copies per milliliter. A total of 11 patients received foscarnet therapy, of 10 patients responded well to the treatment and maintained no recurrence. But 1 patient had a poor response to foscarnet therapy. Except for this patient, the mean hemoglobin level gradually increased from 68.5±9.3 g/L to 73.2±8.8 g/L, and the mean percentage of reticulocytes steadily increased from 0.1±0.0% to 7.6±2.9% after foscarnet therapy. The median serum genome copy number of parvovirus B19 decreased from 9.8 log10 to 6.1 log10 copies per milliliter. There was no significant difference (P=0.61, 0.60) in serum creatinine and glomerular filtration rate before and after foscarnet treatment. At the latest follow-up, the mean hemoglobin was 131.5±12.5 g/L and the hemoglobin correction occurred in all patients. CONCLUSION: Foscarnet therapy doesn't seem to be worse than IVIG for PVB19-PRCA in KTR, and it can be an alternative option.

Application of Metagenomic Next-Generation Sequencing to Diagnose Pneumocystis jirovecii Pneumonia in Kidney Transplantation Recipients.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is one of the common opportunistic infections diagnosed in kidney transplantation recipients. It is difficult to identify early by use of classic tools such as Grocott-Gomori stains and polymerase chain reaction (PCR). Metagenomic next-generation sequencing (mNGS) is accurate, unbiased, and sensitive, and is promising in PJP diagnosis. MATERIAL AND METHODS Data on kidney transplantation patients diagnosed with PJP were retrospectively analyzed. The sensitivity and specificity of different tools such as mNGS, laboratory tests, and Grocott-Gomori stains for PJP diagnosis were compared. All recipients were treated with trimethoprim-sulfamethoxazole (TMP-SMX). RESULTS There were a total of 12 kidney transplantation recipients diagnosed with PJP based on mNGS in our center from January 01, 2020 to October 27, 2020. Highly variable numbers of sequence reads for P. jiroveci (19 to 1041285) showed diagnostic significance. Bronchoalveolar lavage fluid (BALF) samples were tested by Grocott-Gomori staining, with only 6 of 11 (54.5%) positive. Other routine laboratory tests like routine blood tests, blood biochemistry, procalcitonin (PCT), immune function, (1,3)-ß-d-glucan (BG), serum galactomannan (GM), and C-reactive protein (CRP) showed even lower efficacy. TMP-SMX appeared to be the ideal therapy for kidney transplantation recipients with PJP. CONCLUSIONS mNGS has utility in the diagnosis of PJP and mixed infections in kidney transplantation recipients, and TMP-SMX could be the ideal therapeutic drug for kidney transplantation recipients suffering from PJP.

Perfect outcome of kidney recipients with ureteral stenosis after treatment with open surgery under magnetic resonance urography localization.

BACKGROUND: To evaluate the outcome of kidney recipients with ureteral stenosis after treatment with open surgery under magnetic resonance urography (MRU) localization. METHODS: We assessed 2,256 consecutive kidney transplant recipients between October 2010 and December 2018. Ureteral stenosis was detected by ultrasound, confirmed and positioned by Magnetic Resonance Urography. All patients underwent open ureteral reconstruction. The ureteral stenosis was located according to the location on the MRU during the operation. Surgical complications and recurrence rate were recorded in the stenosis group. Outcomes were compared with those of a matched control group of transplant recipients with no history of ureteric stenosis. RESULTS: The incidence of ureteral stenosis in our center was 3.1% (70/2,256). Sixty-four cases (91.4%) were confirmed to have distal stenosis and were reconstructed with ureterovesical re-implantation; six cases (8.6%) were confirmed to have mid-distal stenosis and were subjected to ureteroureterostomy with the use of native ureter. The overall success rate was 100% and the graft function was salvaged in all cases. There was no recurrence of stenosis after a mean follow-up of 38.9±26.3 months. The complication rate was 5.7%. The 110-month graft survival and patient survival were not significantly different between the stenosis and control groups.Conclusions: MRU is an effective method for non-invasive and accurate diagnosis of ureteral stenosis in kidney transplant recipients. Open ureteral reconstruction surgery under MRU localization for treatment of ureter stenosis after kidney transplantation had a high success rate, low recurrence rate and high safety.

Induction therapy with mesenchymal stromal cells in kidney transplantation: a meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications. METHODS: PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. RESULTS: Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46-0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41-1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95-1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21-1.38, P = 0.2) and renal graft function at 1 month (MD = -1.56, 95% CI: - 14.2-11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: - 5.63-5.93, p = 0.96), 6 months (MD = - 1.95, 95% CI: - 9.87-5.97, p = 0.63), and 12 months (MD = - 1.13, 95% CI: - 7.16-4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable. CONCLUSION: Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.

Kidney transplantation from small pediatric donors may be feasible to those who developed chronic refractory dialysis hypotension: a single-center experience.

BACKGROUND: Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. METHODS: Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. RESULTS: There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. CONCLUSIONS: kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.

Comparison of Graft Outcome Between Donation After Circulatory Death and Living-Donor Kidney Transplantation.

BACKGROUND: Donation after cardiac death (DCD) and living-donor (LD) kidney transplantation are the main kidney transplantation types in China. But the outcome of DCD kidney transplantation compared with LD kidney transplantation remains unclear. METHODS: In this study, 325 DCD and 409 LD kidney transplantations were included. We retrospectively compared 3-year graft survival, death-censored graft survival, recipient survival, and graft function. All kidneys of the DCD group were procured from voluntary donation after the citizens' death by the Organ Procurement Organization (OPO) in the presence of the Red Cross, and the transplantation application was approved by the Organ Transplant Ethics Committee. RESULTS: The graft function at year 3 in the DCD group was superior to that of the LD group (eGFR: 71.14±22.28 vs 64.29±16.76 mL/min/1.73 m2; P < .001). After matching donor age, there was no significant difference between the paired DCD and LD group (eGFR: 62.22±18.50 vs 66.99±17.81 mL/min/1.73 m2; P = .068). The 3-year graft survival (94.7% vs 97.4%; P = .041) and recipient survival (97.2% vs 99.5%; P = .011) were a little worse in the total DCD group. However, once the DCD kidney transplantation recipients survived more than 2 months, graft and recipient survival rates were similar between the DCD and LD groups (97.7% vs 97.4%, P = .866 and 99.5% vs 99.0%, P = .466). These results were confirmed in an age-paired groups study. Severe infection was the main cause of graft loss and recipient death in the early stage of DCD transplantation. CONCLUSIONS: Medium- and long-term graft function of DCD kidney transplantation were comparable to LD kidney transplantation. Our results supported the continued use of DCD kidneys.

Successful repair of kidney graft artery rupture secondary to infection using a preprocessed homologous "Y"-shaped iliac artery.

OBJECTIVES: This retrospective study aims to describe novel ways of repair kidney allograft artery rupture secondary to infection using a preprocessed homologous "Y"-shaped iliac artery. METHODS: Five patients' whose course was complicated by graft arterial rupture were included in the rupture group, and patients who received the kidney from the same donor were included in the control group. In the rupture group, the iliac artery used for revascularization was harvested from a DCD donor, pre-treated with absolute diethyl ether, followed by absolute alcohol, and then preserved in 75% alcohol. A biopsy of the arterial graft was obtained and stained using hematoxylin and eosin (H&E). Once a patient was diagnosed with kidney allograft arterial rupture by ultrasound, emergency surgery was conducted and the preprocessed "Y"-shaped iliac artery was used for bridging. RESULTS: Five patents were included in the rupture group. The "Y"-shaped iliac artery grafts were successfully preprocessed, H&E staining and electron microscope observation revealed few visible nuclei, with karyorrhexis and karyolysis. There were no significant differences in the long-term graft survival between two groups. CONCLUSIONS: In conclusion, using preprocessed homologous "Y"-shaped iliac artery provides a useful method to bridge the vascular defects from kidney graft artery rupture secondary to infection in renal allograft recipients.

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study.

Donor-derived cell-free DNA (ddcfDNA) is reported to be a promising noninvasive biomarker for acute rejection in organ transplant. However, studies on monitoring ddcfDNA dynamics during the early periods after organ transplantation are scarce. Our study assessed the dynamic variation in ddcfDNA in early period with various types and status of kidney transplantation. Target region capture sequencing used identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level was 20.69% at the initial time post-transplant, and decreased to 5.22% on the first day and stayed at the stable level after the second day. The ddcfDNA level in DCD (deceased donors) group (44.99%) was significantly higher than that in LDRT (living donor) group (10.24%) at initial time, P < 0.01. DdcfDNA level in DGF (delayed graft function) recipients was lower (23.96%) than that in non-DGF (47.74%) at the initial time, P = 0.89 (19.34% in DGF and 4.46% in non-DGF on the first day, P = 0.17). DdcfDNA level at initial time significantly correlated with serum creatinine (r2  = 0.219, P = 0.032) and warm ischemia time (r2  = 0.204, P = 0.040). Plasma ddcfDNA level decreased rapidly follow an L-shaped curve post-transplant, and level in DGF declined slower than non-DGF. The rebound of ddcfDNA level may indicate the occurrence of acute rejection.

Hemodialysis or Peritoneal Dialysis, Which Is Better for Patients with Delayed Graft Function?

BACKGROUND/AIMS: Hemodialysis (HD) or peritoneal dialysis (PD) is an important renal replacement method in patients with delayed graft function (DGF) after kidney transplantation; however, it is not clear which dialysis modality is superior. This study determined the impact of different dialysis modalities on patients with DGF. METHODS: It was a single-center, retrospective and descriptive study. We performed 673 kidney transplants from donors after cardiac death (DCD) between January 2010 and December 2016 at our center and 138 (20.5%) recipients developed DGF after transplantation. We classified the recipients into two groups according to post-transplant dialysis: DGF-HD (n=96) and DGF-PD (n=42). We analyzed the outcomes of the different dialysis modalities 30 days and 1 year post-transplantation. RESULTS: There were no differences in baseline factors between patients with post-transplant HD (n = 96) or PD (n = 42). There were 10 patients with conversion from PD to HD during DGF. The DGF-PD patients had a higher rate of treatment failure than the DGF-HD patients (23.8% vs. 0%, p < 0.001), peritonitis (7.1% vs. 0%, p = 0.027), and longer duration of dialysis dependence (10.5 vs. 9 days, p = 0.003). There was no statistically significant difference between both groups with respect to acute rejection, hemorrhage, and patient and graft survival at 1 year. CONCLUSION: In renal transplant recipients with DGF, post-transplant PD led to increased treatment failure. PD did not result in rapid recovery of transplanted renal function, and had a high probability of peritonitis.

Short-Term Intensified Dosage Regimen of Mycophenolic Acid is Associated with Less Acute Rejection in Kidney Transplantation from Donation after Circulatory Death.

INTRODUCTION: Whether an early, short-term, adequate exposure to mycophenolic acid (MPA) under tacrolimus-based immunosuppression regimen in kidney transplantation from donation after circulatory death (DCD) was effective and safe is yet unknown. MATERIAL AND METHODS: The study was a single-center, retrospective, cohort study of DCD transplantation in China. Intensified and standard dosage regimens of enteric-coated mycophenolate sodium (EC-MPS) were week 1, 2,160 vs. 1,440 mg/day. The incidences of biopsy-proven acute rejection (BPAR), delayed graft function, infection, and patient and graft survival were compared between the 2 groups. RESULTS: A total of 209 patients (n = 82 in intensified group and n = 127 in standard group) were enrolled from August 2013 to December 2014. The incidence of BPAR at 12 months was significantly lower in the intensified group as compared to that of the standard group. (2.4 vs. 10.2%, p = 0.035). The mean MPA area under curve (AUC) levels at day 7 was significantly higher in the intensified group than that in the standard group (66.18 ± 35.48 vs. 45.30 ± 23.5 mg·h/L, p < 0.001). MPA AUC levels were significantly decreased in patients with BPAR as compared to those with NO-BPAR. CONCLUSION: An early, short-term regimen of intensified EC-MPS with tacrolimus increased early MPA exposure and achieved a low rate of BPAR in kidney transplantation from DCD.

Urinary C­X­C motif chemokine 13 is a noninvasive biomarker of antibody­mediated renal allograft rejection.

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C­X­C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody­mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid­resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Noninvasive detection of acute renal allograft rejection by measurement of soluble Tim-3 in urine.

The purpose of the present study was to assess whether urinary soluble T-cell immunoglobulin and mucin domain-containing protein 3 (sTim-3) could be adopted as a novel non­invasive biomarker for acute rejection (AR) following renal transplantation. A total of 156 patients were enrolled between January 2006 and December 2009, comprising 49 patients with biopsy­proven AR, 58 patients with stable grafts and no abnormal histological findings (NO­AR), 10 patients with subclinical rejection (SCR) in protocol biopsies, 10 patients with acute tubular necrosis (ATN) and 29 patients with chronic allograft nephropathy (CAN). Additionally, urine samples from 40 healthy individuals were also collected as controls. The urinary concentration of sTim­3 was determined by ELISA in the 156 renal allograft recipients and 40 healthy controls. Compared with NO­AR and healthy controls, patients with AR excreted urinary sTim­3 at a significantly higher level (4,356±440.4, 95% CI: 3,473­5,242 ng/mmol creatinine). Likewise, patients with ATN exhibited a significantly lower level of urinary sTim­3 (2,060±217, 95% CI: 1,679­2,680 ng/mmol creatinine) than patients with AR. The discriminatory value was measured by the area under the receiver operating characteristic curve (ROC), which had a value of 0.88 (95% CI: 0.809­0.951), demonstrating that sTim­3 was a suitable marker for the diagnosis of AR. At a cut-off point of 1,836 ng/mmol creatinine, the sensitivity was 89.8% and the specificity was 82.8% (P<0.001). Amongst the patients with AR, patients with steroid­resistant acute rejection (n=31) had significantly higher urinary sTim­3 concentrations than patients with steroid­sensitive acute rejection (n=18; 5,548±613.5, 95%CI: 4,287­6,809 ng/mmol creatinine vs. 2,653±391.7, 95% CI: 1,830­3,476 ng/mmol creatinine; P=0.0002). No significant difference in urinary sTim­3 was found between patients with AR and CAN (3,920±543.5, 95% CI: 3,473­5,242 ng/mmol creatinine), and a significantly higher level of Tim­3 was excreted by patients with CAN compared with patients with NO­AR and healthy controls (P<0.001). The present study, therefore, suggests that urinary sTim­3 may be used as a valuable non­invasive biomarker for the detection of AR. In addition, urinary sTim­3 levels were demonstrated to be associated with the response to anti­rejection therapy. The results of the present study may provide support future research into the screening of novel immune suppressants.

Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function.

BACKGROUND: Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. METHODS: We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. RESULTS: The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m2 in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 µmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. CONCLUSION: Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection.

Evaluation of the area under the curve of enteric-coated mycophenolate sodium using a limited sampling strategy in Chinese kidney transplant recipients
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AIMS: To investigate the area under the curve (AUC) of mycophenolic acid (MPA) in adult Chinese renal allograft recipients receiving concomitant enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine (CsA) during the early post-transplant phase and to develop optimal model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12h) using a limited-sampling strategy (LSS). METHODS: The present study enrolled 24 Chinese renal recipients treated with EC-MPS, CsA, and corticosteroid, from whom 24 serial blood samples were collected over 12 hours. MPA concentration was evaluated with enzyme multiplied immunoassay technique (EMIT). LSS was developed by multiple stepwise regression analysis using a two-group method (test group, n = 12; and validation group, n = 12). RESULTS: The MPA predose concentration had a poor correlation with MPA AUC0-12h, and the best equations obtained from the test group were the following: 25.73 + 0.59 × C1.5 + 0.79 × C2 + 2.03 × C4 (for three time points, r2 = 0.761) and 22.13 + 1.7 × C0.5 + 0.61 × C1.5 + 0.78 × C2 + 1.83 × C4 (for four time points, r2 = 0.853). When these equations were tested in the validation group, there were no significant differences in prediction errors. CONCLUSION: An LSS using time points at 1.5, 2, and 4 hours or 0.5, 1.5, 2, and 4 hours provides the most accurate and reliable estimation of the MPA AUC0-12h in Chinese adult renal recipients treated concomitantly with EC-MPS and CsA during the early post-transplant phase.
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